The clinical importance of serum urokinase plasminogen activator receptor and carbonic anhydrase IX levels and the effect of anthracycline-based adjuvant chemotherapy on these biomarkers in breast cancer

J Cancer Res Ther. 2018 Apr-Jun;14(3):608-613. doi: 10.4103/0973-1482.174547.


Introduction: Breast cancer mortality rates after metastasis is high. Urokinase plasminogen activator receptor (uPAR) and carbonic anhydrase IX (CAIX) play very important roles during tumor cell invasion and metastasis. The purpose of this study was to evaluate plasma levels of uPAR and CAIX and the effect of anthracycline-based chemotherapy on these biomarkers in patients with operable breast cancer.

Materials and methods: Sixty-five patients and 25 age-matched healthy controls were enrolled. Levels of uPAR and CAIX were investigated before and after adjuvant chemotherapy. Basal (prechemotherapy) uPAR and CAIX levels in patients were compared with those in healthy controls and in patients after 3 cycles of chemotherapy. Levels of uPAR and CAIX were determined using the ELISA method.

Results: uPAR and CAIX levels were significantly higher in patients (P: 0.02 and P: 0.03, respectively). Postchemotherapy uPAR and CAIX levels were higher than basal levels (P: 0.645 and P < 0.001, respectively). A cut-off value of 27.99 pg/mL for uPAR was associated with 45.31% sensitivity and 84.62% specificity, and with a positive predictive value (PPV) of 87.9% and a negative predictive value (NPV) of 38.6%. A cut-off value of 777.84 pg/mL for CAIX was associated with 90.62% sensitivity and 30.77% specificity, and with a PPV of 76.3% and an NPV of 57.1%.

Conclusion: We determined that uPAR and CAIX levels were higher in the fluorouracil, epirubicin, and cyclophosphamide (FEC) chemotherapy group than in the control group, but there was no difference between the FEC and epirubicin/adriamycin chemotherapy groups in terms of basal and postchemotherapy uPAR, CAIX levels. Furthermore, uPAR is more specific, and CAIX is more sensitive in the diagnosis of breast cancer.

Keywords: Breast cancer; carbonic anhydrase IX; thrombosis; urokinase plasminogen activator.

MeSH terms

  • Adult
  • Aged
  • Anthracyclines / administration & dosage
  • Antigens, Neoplasm / blood*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / blood*
  • Breast Neoplasms / blood*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Carbonic Anhydrase IX / blood*
  • Case-Control Studies
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Epirubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Prognosis
  • Receptors, Urokinase Plasminogen Activator / blood*
  • Survival Rate


  • Anthracyclines
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Receptors, Urokinase Plasminogen Activator
  • Epirubicin
  • Doxorubicin
  • Cyclophosphamide
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Fluorouracil